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New Biomarkers Predict Outcome of Cancer Immunotherapy

By Labmedica International staff writersPosted on 25 Jan 2018

Image: Cytometry by time of flight (Cy-TOF) cell analysis apparatus (Photo courtesy of the University of Minnesota).

Melanoma and lung cancer can be combatted effectively through immunotherapy, which makes targeted use of the immune system's normal function of regularly examining the body's tissue for pathogens and damages.

Specific inhibitors are used to activate immune cells in a way that makes them identify cancer cells as foreign bodies and eliminate them. This way, the immune system can boost its often weak immune response to allow it to even detect and destroy metastatic cancer cells.

Scientists at the University of Zurich (Zurich, Switzerland) and their colleagues examined biomarkers in 40 blood samples of 20 patients, both before and 12 weeks after immunotherapy. For this, they used the high-dimensional "cytometry by time of flight" (Cy-TOF) cell analysis method, which analyzes cells for up to 50 different proteins one cell at a time. The team was able to differentiate every single cell and document its activation status and even nuanced differences between the patient samples were recorded in detail.

The investigators, observed that during therapy a clear response to immunotherapy in the T cell compartment. However, before commencing therapy, a strong predictor of progression-free and overall survival in response to anti-PD-1 immunotherapy was the frequency of CD14+CD16-HLA-DRhi monocytes. They confirmed this by conventional flow cytometry in an independent, blinded validation cohort, and they propose that the frequency of monocytes in peripheral blood monocytes (PBMCs) may serve in clinical decision support. For the finding to be easily verifiable the biomarkers should be easily detectable; indeed, the blood count was able to be validated using conventional methods in a second, independent cohort of more than 30 people.

Burkhard Becher, PhD, a professor of Immunology and the senior author of the study, said, “Even before the start of a therapy, we observed a subtle and weak immune response in the blood, and identified this molecular pattern as the immune cells CD14+CD16-HLA-DRhi.” The study was published on January 8, 2018, in the journal Nature Medicine.